DEFENCE AGAINST INFECTION

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Infection in cancer
and transplantation

Evolving antimicrobial resistance has resulted in

significant variation in pathogen susceptibility between
regions; as a consequence, empirical therapy regimens
vary between centres

Rick Holliman

In febrile neutropenia, some authorities now

recommend broad-spectrum monotherapy instead
of a combination of agents; this approach remains
controversial
Oral therapy can be considered in septic
immunocompromised patients who are at low risk of
death

In the healthy state, the human body is protected from infection by

a range of mechanisms including cellular and humoral immunity,
mechanical barriers (skin and mucus membranes), complement,
phagocytes and the effects of normal bacterial flora. Defects in
one or more of these protective mechanisms are associated with
characteristic infection patterns. Specific disease states have an
established effect on certain aspects of body defences, such that the
likely causes of opportunistic infection can be predicted. Examples
of these associations are shown in Figure 1.

Use of sterile food in profoundly immunosuppressed

patients has largely been abandoned in favour of lowrisk diets

Sequence of infections

Management

Infections in the immunocompromised often follow temporal

patterns resulting from evolution of the immune defects and the
timing of specific therapeutic interventions.
Profound neutropenia and mucositis develop 10 days after
cytotoxic therapy, when Gram-negative septicaemia and vascular
line-related infections are most common.
When the granulocyte count recovers, usually after several
weeks, acute graft-vs-host disease (GvHD) and deranged cellmediated immunity are associated with cytomegalovirus (CMV),
adenovirus and fungal infection.
Chronic GvHD may develop after 3 months, accompanied by
varicella-zoster, CMV and Pneumocystis jiroveci (previously known
as P. carinii) infection.
Persistent antibody defects can result in overwhelming pneumococcal infection months or years after the initial chemotherapy.

The range of potential pathogens is wide and progression of infection can be extremely rapid in immunocompromised patients.
Consequently, early empirical therapy is recommended using
combinations of antibiotics to achieve an adequate spectrum of activity. Extended-spectrum -lactams (e.g. piperacillin, tazobactam),
aminoglycosides (amikacin) and carbapenems (meropenem) are
often used. Choice of agents should be based on local resistance
patterns, and some units find it helpful to screen patients routinely, tailoring subsequent therapy to cover any resistant flora
detected.
Antimicrobial combinations are used sequentially to cover
possible infection patterns, starting with the most common and
most virulent pathogens such as Gram-negative bacteria. Thus,
treatment for coagulase-negative staphylococci and fungal infection
may be introduced 24 days after the onset of fever, and only when
the patient fails to respond to initial therapy for Gram-negative
sepsis. However, empirical regimens should always be modified
in light of specific findings on examination or investigation, or
positive microbiological results. Some authorities now recommend
broad-spectrum monotherapy instead of a combination of agents in
febrile neutropenia.1 However, this approach remains controversial.
Oral therapy can be considered in septic immunocompromised
patients who are at low risk of death.2
Duration of therapy is not well established and treatment is
often given until immune reconstitution occurs or for an arbitrary
period after a complete response.

Diagnosis of infection
A thorough physical examination is required, with particular
attention to the oropharynx, lungs, skin, vascular line sites and
perianal area. CT is more sensitive than radiography for detecting lung infections, particularly with Aspergillus. Bronchoaveolar
lavage, blood culture and buffy coat (for CMV) are the most useful
microbiological studies. Antibody-based assays are of limited value.
Antigen-detection methods are improving but lack sensitivity.

Prevention of infection
Hygiene: strict hygiene based largely on handwashing is necessary to prevent immunocompromised patients becoming infected
with pathogens carried by health-care staff or visitors. Masks,
gowns and gloves are often used, but their value is less certain.
Laminar airflow and high-efficiency particulate air-filtered rooms
are recommended for bone marrow transplant units. Sterile diets

Rick Holliman is Reader and Consultant in Clinical Microbiology at

St Georges Hospital and Medical School, London, UK. He qualified
from St Marys Hospital, London, and trained in clinical microbiology in
London and Stanford, USA. His research interests include infections in
immunocompromised and intensive care patients, antibiotic resistance
and toxoplasmosis.

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2005 The Medicine Publishing Company Ltd

DEFENCE AGAINST INFECTION

Characteristic infections in immunocompromised patients

Disease state

Defective defence mechanism

Pathogens

Central lines, burns, trauma

Skin and vascular catheters

Staphylococcus aureus, coagulase-negative staphylococci,

Pseudomonas spp., Corynebacterium spp., Streptococcus
pyogenes, Candida spp.

Cytotoxic drugs, radiation

Mucositis

Viridans group streptococci, Candida spp., herpes simplex virus

Cytotoxic drugs, radiation,

corticosteroids, lymphoma,
chronic leukaemia

Lymphocytes

Varicella zoster virus, cytomegalovirus, Pneumocystis jiroveci,

Candida spp., Toxoplasma gondii, EpsteinBarr virus

Cytotoxic drugs, radiation,

corticosteroids, acute leukaemia

Neutrophils

Gram-negative aerobic bacteria (e.g. Pseudomonas),

Staphylococcus aureus, cytomegalovirus, Aspergillus spp.,
Candida spp., Pneumocystis jiroveci

have largely been replaced with low-risk food, but home-cooked

foods are not advised and fresh flowers and plants should not be
placed in the patients room.

FURTHER READING
Cainello F, Vento S. Infections and solid organ transplant rejection:
a cause-and-effect relationship? Lancet Infect Dis 2002; 2: 53949.
Hagerty J A, Ortiz J, Reich D et al. Fungal infections in solid organ
transplant patients. Surg Infectt 2003; 4: 26371.
Mandell G L, Bennett J E, Dolin R, eds. Principles and practice of
infectious diseases. 5th ed. Edinburgh: Churchill Livingstone, 2000.
Montoya J G, Giraldo L F, Efron B et al. Infectious complications among
620 consecutive heart transplant patients at Stanford University
Medical Center. Clin Infect Dis 2001; 33: 62940.
Nichols W G. Management of infectious complications in the
haematopoietic stem cell transplant recipient. J Intensive Care Med
2003; 18: 295312.
Viscoli C. Management of infection in cancer patients. Studies of the
EORTC International Antimicrobial Therapy Group (IATG). Eur J Cancer
2002; 38: S827.

Immunization against selected pathogens is feasible, but the

response to the vaccine is often suboptimal. Immunoglobulin
can be given to protect immunocompromised patients following
exposure to chicken pox.
Prophylactic antimicrobial therapy: antifungal prophylaxis using
azoles is well established, but the role of antibacterial prophylaxis
is controversial, with few adequate trials. However, many bone
marrow transplant units use oral quinolone prophylaxis. Prophylactic trimethoprimsulfamethoxazole is effective in preventing
Pneumocystis infection following organ transplantation, and
aciclovir reduces the incidence of herpes simplex and varicellazoster virus infection.
Gut decontamination: the gastrointestinal tract is the source of
many infections in immunocompromised patients, and numerous
attempts have been made to reduce endogenous flora using oral,
non-absorbable antimicrobial agents including framycetin, colistin
and neomycin. These pastes and mixtures are unpalatable and
compliance is often poor.

Practice points
Infections in immunocompromised patients often follow
predictable epidemiological patterns associated with the
specific immune defect
Specific infections may appear at distinct times in the course
of the immunosuppressed state
Diagnosis requires focused examination, radiology and
microbial detection methods
Management is based on empirical therapy defined by local
epidemiological data
Multiple interventions are used to reduce the incidence of
infection, but the relative value of these measures is unclear

REFERENCES
1 Paul M, Somres-Weiser K, Grozinsky S et al. Beta-lactam versus
beta-lactamaminoglycoside combination therapy in cancer patients
with neutropenia. Cochrane Database Syst Revv 2002; 3: CD003038.
2 Vidal L, Paul M, Ben Dor I et al. Oral versus intravenous antibiotic
treatment for febrile neutropenia in cancer patients: a systematic
review and meta-analysis of randomized trials. J Antimicrob
Chemotherr 2004; 54: 2937.

MEDICINE 33:3

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2005 The Medicine Publishing Company Ltd